Barrier Formation: Potential Molecular Mechanism of Enamel Fluorosis
Barrier Formation: Potential Molecular Mechanism of Enamel Fluorosis
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DOI：
10.1177/0022034513510944
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发表时间：
2014-01-01
影响因子：
7.6
通讯作者：
Bronckers, A. L. J. J.
中科院分区：
文献类型：
--
作者：
Lyaruu, D. M.;Medina, J. F.;Bronckers, A. L. J. J.
氟牙釉质症是一种在釉质形成过程中暴露于超适宜水平的氟而导致的不可逆的釉质结构性缺陷。我们假设氟中毒与矿化釉质基质中形成高矿化线过程中质子的过量释放有关。我们通过分析野生型小鼠和阴离子交换剂-2a，B（Ae 2a，B）缺陷小鼠的氟斑牙釉质缺陷来测试这一概念，Ae 2a，B是成熟成釉细胞中的一种跨膜蛋白，可将细胞外Cl-交换为碳酸氢盐。缺陷在氟中毒Ae 2a，B（-/-）小鼠中比在氟中毒杂合子或野生型小鼠中更明显。表型包括高矿化表面，广泛的亚表面低矿化，和多个高矿化线更深的釉质。所有氟暴露小鼠和Ae 2a，B（-/-）小鼠的矿物质含量均降低，且与Cl-密切相关。暴露的釉质表面下的成熟阶段的成釉细胞的pH指示剂染料表明存在扩散障碍的氟斑牙釉质。这些结果支持的概念，氟化物刺激矿化前沿的超矿化。这导致质子的释放增加，成釉细胞通过分泌更多的碳酸氢盐来响应，以牺牲釉质中的Cl-水平为代价。氟化物诱导的高矿化线可形成阻碍蛋白质和矿物质离子扩散到次表层的屏障，从而延迟生物矿化并导致釉质基质蛋白的保留。
Enamel fluorosis is an irreversible structural enamel defect following exposure to supraoptimal levels of fluoride during amelogenesis. We hypothesized that fluorosis is associated with excess release of protons during formation of hypermineralized lines in the mineralizing enamel matrix. We tested this concept by analyzing fluorotic enamel defects in wild-type mice and mice deficient in anion exchanger-2a,b (Ae2a,b), a transmembrane protein in maturation ameloblasts that exchanges extracellular Cl- for bicarbonate. Defects were more pronounced in fluorotic Ae2a,b(-/-) mice than in fluorotic heterozygous or wild-type mice. Phenotypes included a hypermineralized surface, extensive subsurface hypomineralization, and multiple hypermineralized lines in deeper enamel. Mineral content decreased in all fluoride-exposed and Ae2a,b(-/-) mice and was strongly correlated with Cl-. Exposure of enamel surfaces underlying maturation-stage ameloblasts to pH indicator dyes suggested the presence of diffusion barriers in fluorotic enamel. These results support the concept that fluoride stimulates hypermineralization at the mineralization front. This causes increased release of protons, which ameloblasts respond to by secreting more bicarbonates at the expense of Cl- levels in enamel. The fluoride-induced hypermineralized lines may form barriers that impede diffusion of proteins and mineral ions into the subsurface layers, thereby delaying biomineralization and causing retention of enamel matrix proteins.